The short-chain fatty acid uptake fluxes by mice on a guar gum supplemented diet associate with amelioration of major biomarkers of the metabolic syndrome

Abstract

Studies with dietary supplementation of various types of fibers have shown beneficial effects on symptoms of the metabolic syndrome. Short-chain fatty acids (SCFAs), the main products of intestinal bacterial fermentation of dietary fiber, have been suggested to play a key role. Whether the concentration of SCFAs or their metabolism drives these beneficial effects is not yet clear. In this study we investigated the SCFA concentrations and in vivo host uptake fluxes in the absence or presence of the dietary fiber guar gum. C57Bl/6J mice were fed a high-fat diet supplemented with 0%, 5%, 7.5% or 10% of the fiber guar gum. To determine the effect on SCFA metabolism, 13C-labeled acetate, propionate or butyrate were infused into the cecum of mice for 6 h and the isotopic enrichment of cecal SCFAs was measured. The in vivo production, uptake and bacterial interconversion of acetate, propionate and butyrate were calculated by combining the data from the three infusion experiments in a single steady-state isotope model. Guar gum treatment decreased markers of the metabolic syndrome (body weight, adipose weight, triglycerides, glucose and insulin levels and HOMA-IR) in a dose-dependent manner. In addition, hepatic mRNA expression of genes involved in gluconeogenesis and fatty acid synthesis decreased dose-dependently by guar gum treatment. Cecal SCFA concentrations were increased compared to the control group, but no differences were observed between the different guar gum doses. Thus, no significant correlation was found between cecal SCFA concentrations and metabolic markers. In contrast, in vivo SCFA uptake fluxes by the host correlated linearly with metabolic markers. We argue that in vivo SCFA fluxes, and not concentrations, govern the protection from the metabolic syndrome by dietary fibers.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Effect of dietary supplementation with guar gum on mouse physiology after 6 weeks on a high-fat diet.

(A) Body weight for the different guar gum groups. (B) Adipose weight body weight ratio (AW/BW) for the different guar gum groups. Triglycerides in plasma (C) and liver (D). Plasma glucose (E) and insulin (F) levels after a 4-hour fast. Blood glucose and insulin levels were used to determine insulin sensitivity through HOMA-IR (G). (H) Average glucose infusion rates needed to maintain euglycemic conditions during hyperinsulinemic-euglycemic clamps (HIEC) conditions for the 0% and 10% guar gum groups. (I) Hepatic glucose production (Ra) and peripheral glucose disposal (Rd) rate during HIEC conditions. (J) Cecal content and (K) cecal SCFA concentrations. Data represent means ± SEM for n = 7–8. Different letters indicate significant differences between groups (at least p

Figure 2. Cecal SCFA concentrations correlations.

Correlation of cecal acetate, propionate and butyrate concentration with body weight (A), AW/BW (B), hepatic triglycerides (C) and HOMA-IR (D). The Spearman's correlation coefficient was calculated and the significance level was set at p

Figure 3. In vivo SCFA fluxes.

(A) Enrichment of cecal SCFAs after 6 h infusion with [1-13C] acetate, [2-13C] propionate or [2,4-13C2] butyrate for the different guar gum groups. (B) Schematic overview of the model used to determine in vivo bacterial SCFA production, interconversion and host uptake fluxes at steady state. Each reaction is represented by a flux (v, for a detailed description see Text S1). (C) In vivo SCFA production and uptake fluxes for the different guar gum groups after 6 weeks on high-fat diet. Data represent means ± SEM for n = 7–8. Different letters indicate significant differences between groups (at least p<0.05).

Figure 4. In vivo SCFA uptake fluxes correlate inversely with metabolic syndrome markers.

Correlation of acetate, propionate and butyrate host uptake fluxes with body weight (A), AW/BW (B), hepatic triglycerides (C) and HOMA-IR (D). The Spearman's correlation coefficient was calculated and the significance level was set at p